Neuropeptides

Neuropeptides

1. What are neuropeptides

   • Small protein like molecules
     • 3-30 aa
   • Synthesised from larger precursors
     • At least 90 aa
     • Removal of signal sequence, cleavage events and disulphide bond formation
     • In some cases a single precursor molecular can give rise to multiple bioactive peptides
   • Used by neurones to communicate with each other
   • More than 100 different neuropeptides identified in the mammalian brain
   • Expressed and released by neurones
   • Mediate or modulate neuronal communication by acting on cell surface receptors e.g. GPCRs
   • Act as neuronal signalling molecules, influencing particular brain functions e.g. learning and memory

2. Properties

   • Synthesised as a large precursor molecule at the cell soma
   • Transported to release sites in dense core vesicles
   • Slow postsynaptic effects
   • Actions terminated by extracellular proteases or by diffusion
   • Can trigger complex coordinated behaviours
   • Actions do not require point to point synaptic connections

3. Differences between NT and neuropeptides

   • Much lower concentrations in vesicles
     • About 10mM compared with 100 mM
   • Much higher affinity for receptors
   • Synthesised from precursors and only used once
   • Released by lower concentraton of Ca2+ away from point of entry
     • Neuropeptides and NT can be released form different parts of the nerve terminal

4. Major neuropeptides of the mammalian brain

   • Substance P
     • Sensory and pain
     • Released from the terminals of specific sensory nerves
     • Found in the brain and spinal cord and is associated with inflammatory processes and pain
     • Coexists with the excitatory NT glutamate in primary afferents that respond to painful stimulation
     • Also associated with anxiety, stress, neurogenesis and nausea
     • Signalling mediated through Neurokinin 1 (NK1) receptors
   • Neurotensin
     • Regulation of release of other peptides
   • Oxytocin
   • Vasopressin
   • Neuropeptide Y
   • alpha-endorphin
   • Met-enkephalin

5. Opoid peptides

   • Two functional pentapeptides identified
     • Enkephalins
   • Three additional longer peptides later identified
     • Endorphins
   • Enkephalins and endorphins found throughout the brain but are not co-localised in the same neurones

6. Degredation

   • Enzymatic
     • Aminopeptidase
     • Neprilysin
     • Insulin degrading enzyme
     • Angiotensin converting enzyme